We have previously shown in the rat that glucose and free fatty acid concentrations in portal blood are important determinants of hepatic metabolism. Feeding gerbils (Meriones unguiculatus) low fat high carbohydrate diets (CHO) results in hypercholesterolemia and hypertriglyceridemia. Replacing 20% of the dietary carbohydrate with saturated fat (coconut oil) (COC) increases or does not alter the level of circulating lipids; when unsaturated fat (safflower oil) (SAF) is used, a significant reduction in the levels of serum cholesterol and triglyceride is observed. Changes parallel to these alterations in serum lipids were found in the following parameters: hepatic high Km glucokinase activity, net hepatic glucose utilization, capability of the isolated perfused gerbil liver to convert labeled glucose to tissue lipid and to very light density lipoproteins and fatty acid synthetase activity measured in mitochondrial supernates. These changes are compatible with differences in hepatic exposure to insulin. We therefore propose to investigate circulating levels of insulin (in the fasted state and after feeding animals carbohydrate (CHO), saturated (COC) and unsaturated fat (SAF) diets). We also propose to investigate whether these dietary factors affect the metabolic fate of free fatty acids in the isolated perfused gerbil liver. After appropriate lengths of time on the diets (CHO, COC, SAF) the livers will be perfused with C14-labeled oleic acid. Fatty acid carbon incorporation into various liver lipids, perfusate lipoprotein, perfused carbohydrate lipid and CO2 will be measured as well as ketone body formation. Finally the metabolism of equivalent loads of various saturated and unsaturated acids (palmitate, linoleate and oleate) will be compared in groups of animals on the different dietary regimens.